Methylphenidate and Related Compounds. Fig. 1. The figure summarizes the dose-response of acute methylphenidate injection on the horizontal activity and the number of stereotypic activities of female and male WKY, SHR, and SD rats, using the open field assay. Each group consists of N=8 and was given saline on experimental day 1 and methylphenidate on experimental day 2. The 0.6 mg/kg methylphenidate failed to elicit any changes in the horizontal activity of female and male WKY and SHR groups, while this low dose of methylphenidate significantly increased the horizontal activity of male SD rats (Fig. 1 - left column). The 2.5 mg/kg methylphenidate given ¡.p., increased significantly (*P< 0.05) only the horizontal activity of male WKY and SD rats and female SHR and SD rats (Fig. 1 - middle column), as compared to that of the saline control group. Female SHR and SD exhibited significantly (A P<0.05) greater increase in activity compared to their male counterparts. The highest methylphenidate dose (10.0 mg/ kg) induced robust increase in locomotor activity when compared to baseline. * - indicates significant (P< 0.05) difference when comparing the animal group to its control day, that is, experimental day 2 to experimental day 1. A indicates significant (P<0.05) difference between the sexes of each rat strain.
Methylphenidate and Related Compounds. Fig. 2. This figure demonstrates behavioral sensitization. The embedded histograms in the upper right corner depict the total change from the baseline activity in the initial 2-h following injection at all administration times. The numbers indicate the experimental days. The figure summarizes 15 consecutive recordings (N=8) of four different locomotor activity indices. The locomotor recording of three control days (baseline) was set arbitrarily as 0. Following the control days, six single daily injections of 2.5 mg/kg methylphenidate (i.p.) were given at 07:00, and followed by 5 days of washout. Finally, a re-challenge injection of 2.5 mg/kg methylphenidate (i.p) was administered on experimental day 15. In all the four locomotor indices, the activity on experimental day 15 was significantly elevated as compared to the recording on experimental day 4 (1st day of methylphenidate injection). In the temporal graphs, the filled circles are the recordings after saline injection, while the squares denote the locomotor activity after 2.5 mg/kg methylphenidate.
psychostimulants by different strains, and the long-term effects of the drug (sensitization or tolerance) can also be different in each strain.
Since no biological marker for ADHD has yet been identified, diagnosis of ADHD is presently based only on behavioral symptoms. Many suggested ► animal models of ADHD exist, including rats selected from a general population, rats reared in social isolation, rats exposed to environmental pollutants, rats that have undergone neonatal anoxia, rats that have undergone hippocampal X-irradiation in infancy, rats that have undergone neurotoxic brain lesions, Naples High/Low excitability rats, and knockout mice. There are also genetic models, including the spontaneously hypertensive/hyperactive rat (SHR) strain, which was bred from progenitor Wistar Kyoto (WKY) rats (Dafny and Yang 2006). The SHR is a rat strain hyperactive in a variety ofbehavioral characteristics that are comparable to the behavior of children with ADHD, including motor and cognitive impulsiveness, impaired sustained attention, hyperactivity, and reduced DA function. Therefore, the SHR strain is used most often in ADHD/methylphenidate studies. Most investigators who study the properties of drugs on animals do so in the belief that their work will ultimately be relevant to people.
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